Inhalation devices which allow a patient to inhale an aerosol are required for numerous medical applications, such as the inhalative treatment of asthma, cystic fibrosis (CF), and a number of other respiratory diseases. An aerosol is a dispersion of small solid particles or liquid droplets in a continuous gas phase. Typically, aerosols of fine droplets of a liquid formulation of a bioactive agent or drug are required in medical inhalation treatments; ideally reaching even the smallest branches of the peripheral lungs, such as bronchioles and alveoli.
In order to achieve the desired homogeneous droplet distribution in the gas phase, the liquid formulation in the inhalation device is atomised by nebulisers, such as ultrasonic nebulizers, jet nebulizers or vibrating mesh nebulizers.
The individual components of currently available vibrating mesh nebulizers, such as, for example, the liquid reservoir, the aerosol generator comprising the vibrating mesh, the mixing chamber and the mouthpiece, are typically assembled so that the nebulizer membrane is either arranged approximately vertical or horizontal.
With vertically arranged nebulizer membranes, the generated aerosol is introduced horizontally into the air flow channel, and the aerosol generator can be positioned at an angle to the direction of the air flow, without thereby changing the vertical arrangement of the membrane. Depending on the selected angle, it is even possible to introduce the aerosol roughly in parallel with the air flow. This approach is, for example, chosen by PARI (e.g. WO 2009/135871 A1) and may, in addition, be complemented with an annular air stream surrounding the aerosol generator so that the nascent aerosol is engulfed in air to avoid particle collision with the inner walls of the mouthpiece. Thereby this “air jacket” as well as the option to orient the aerosol generator at an angle to the direction of the air flow eliminates the need for spacious mixing chambers. However, since the liquid has to be supplied to a vertically positioned nebulizer membrane, even minor handling deviations such as tilting the device during inhalation lead to distinct variations in liquid supply and consequently the volume inhaled as an aerosol. Also, the residual volume remaining in the reservoir at the end of the inhalation treatment is typically higher than for inhalation devices with a horizontally arranged nebulizer membrane. In addition, errors during assembly of the inhalation device as well as the vertical arrangement of the nebulizer membrane commonly create problems with providing airtight, leak-proof connections between the aerosol generator and the air flow channel.
Horizontally arranged nebulizer membranes allow for an easier, gravity-driven and thus less variable supply of the liquid from a reservoir above said membrane. However, the generated aerosol is now introduced perpendicular into the air flow channel, so that typically mixing chambers are required in order to avoid particle collision with each other and/or the device's inner walls and to homogeneously mix the aerosolized particles with the air flow before inhalation by the user. Typically, these mixing chambers are rather spacious and hence increase the dimensions of the inhalation devices unfavourably. Furthermore, owing to longer residence times of the aerosol in the mixing chamber and turbulences within said mixing chamber sedimentation and impaction of the aerosolized particles occur, thereby increasing wastage of the aerosolized formulation as well as decreasing dose reproducibility. Also, the vertically stacked arrangement of liquid reservoir, aerosol generator (with horizontal membrane) and mixing chamber, leads to devices which are rather high compared to their width. This could lead to handling problems because devices may easily fall on their side, especially upon filling of the reservoir or in filled state.
Further problems may arise during the assembly of the nebulizer, when patients put the individual components of the inhalation device together incorrectly, for example, after cleaning and/or disinfecting them as required. This could lead to irreproducible dosing of active agents due to leakage of the liquid, malfunctions such as pressure losses, reduced therapeutic efficacy or even permanent damages to the device. Especially sick and/or elderly users may become discouraged by complicated dissembling-and assembling routines and either stop to comply with their therapy or stop to dissemble and clean their device regularly. This provokes a worsening of symptoms and/or increases the risk for infections of the respiratory tract from contaminated devices.
WO 2008/050542 A1 discloses a portable inhalation device comprising a main body, a detachable mouthpiece, an inkjet system medicine cartridge and a slide-on cover. The main body comprises an air flow path and two fitting portions where the medicine cartridge and the mouthpiece can be inserted in such a way that they are in fluid communication with the air flow path. The medicine cartridge comprises a reservoir (as an integral or detachable part), electrical connectors and an ejection head, preferably equipped with a heater, from which medicine is ejected by thermal energy using the principle of inkjet systems. As an alternative to such electro-thermal ejection means electro-mechanical ejection means are suggested, such as by piezo-electric devices. After its insertion into the fitting portion, the medicine cartridge is fixed to the main body by the slide-on cover.
WO 2008/050542 A1 does not describe key lock members or similar features of the medicine cartridge or of the main body which would ensure easy and correct assembly, i.e. the complete insertion of the medicine cartridge in the right orientation, and securely lock the components together. Furthermore, the first segment of the mouthpiece in WO 2008/050542 A1 (i.e. the communicating portion which is inserted into the main body) does not comprise a lateral opening for receiving the ejection head of the medicine cartridge. Therefore the aerosol is emitted directly into the air flow path of the main body before entering the first segment of the mouthpiece. In this manner, some aerosol will inevitably be deposited within the main body. In consequence, this does not only lead to an increased loss of aerosol, but is also associated with the disadvantage that the user would have to clean not only the detachable mouthpiece but also the air flow path in the opened main body which houses the water-sensitive electronic controls for the ejection head and further electrical components.
WO 2006/083014 A1 describes a similar portable inhaling apparatus comprising a main body provided with a fitting section for removably fitting thereto a disposable liquid agent ejection cartridge. The ejection cartridge comprises a storage tank for a liquid agent, an ejection head with ejection means, an integral mouthpiece (called suction port) and a flow path projecting from the cartridge. The ejection head may be an ink-jet head comprising a heater or a piezoelectric element or one having a mesh structure with a large number of pores. The mouthpiece is an integral part of the ejection cartridge, as favoured by the authors, and therefore the mouthpiece must be discarded along with the cartridge every time the storage tank is empty, as the storage tank cannot be effectively cleaned and/or refilled by a user. Moreover, the document is silent about key locks or any other features of this type which would ensure easy, correct and complete assembly of the device. Further, the device does not exhibit a mouthpiece having a lateral opening for receiving an aerosol generator capable of emitting an aerosol into the flow path of the mouthpiece.
It is thus the aim of the current invention to provide an improved inhalation device comprising a low number of components which ensure the fast and correct assembly and filling of the device as well as to improve its air tightness and reduce pressure losses and leakages by reducing the number of leak-prone connections. Another aim of the current invention is to allow for easier, safer cleaning operations. It is further the aim of the current invention to facilitate effective customization by providing inhalation devices comprising aerosol generators which are tailor-made for specific therapies, wherein said aerosol generators can be assembled only with its intended counter-components.